1. Field of Invention
This invention relates generally to the treatment of patients with both a pharmaceutical agent applied topically to the skin and with heat, and more particularly to a combined chemo-thermo therapy technique in which heat acts to accelerate the absorption and diffusion of the agent and to promote its interaction with the tissue in the problem region of the body being treated.
2. Status of Prior Art
The term "problem region," as used herein, refers to a tumor, a set of muscles, or any other tissue site underlying the skin which is causing difficulty and which lends itself to treatment.
The interior of the human body has a normal temperature level which is usually said to be 98.6.degree. F. But actually, in the course of each 24-hour period, the body temperature rises above or falls somewhat below this nominal value. Body temperature is determined by the relationship existing between the amount of heat internally generated, which depends on basal metabolism and the amount of heat escaping from the body. Additional heat is produced as a result of muscular activity, this being dissipated by an increase in radiation, conduction or evaporation from the skin surface and by more rapid and deep breathing.
Medical practitioners since ancient times have known that the application of heat to the body is useful in the relief of muscle soreness and various aches and pains, as well as in the treatment of certain pathological conditions. Thus the use of heat for the treatment of arthritis and other abnormalities is now commonplace. Hot water bottles and electrical heating pads are in widespread use, not merely to provide warmth, but also to afford a degree of relief or therapy for various conditions. In applying heat to the surface of the body, one may do so by convection, by direct contact with a warmed substance; that is, by conduction, or by radiating energy into the body.
As pointed out in chapter 10, "Therapeutic Heat" in the text Therapeutic Heat and Cold, edited by Justuf F. Lehmann and published in 1982 by Williams and Wilkins, it is generally accepted that heat produces desirable therapeutic effects, for it increases the extensibility of collagen tissues, it decreases joint stiffness, and it affords pain relief. Moreover, heat relieves muscular spasms, it aids in the resolution of inflammatory infiltrates, edema and exudates, and it enhances blood flow.
The difficulty heretofore experienced in effectively applying heat to a patient is that when transferring heat inwardly through living tissue to a problem region underlying the skin, if the heat applied to the skin surface is within a tolerable temperature range, then not enough heat energy is transferred to this site to afford beneficial effects.
As indicated in the Lehmann text, superficial heat is commonly tied in with various forms of heating media such as a paraffin bath, hot air or hot water and radiant heat (infrared). For a given patient, the temperature sensitivity threshold is that temperature level of the heating medium to which the patient is exposed, above which the patient experiences undue discomfort. Thus temperature levels of the medium below the sensitivity threshold are more or less tolerable, whereas those above the threshold are effectively intolerable. If, for example, a patient being subjected to thermotherapy finds that the heat is more than he can stand and wishes the procedure discontinued, clearly the heat of the medium to which he is exposed is above his sensitivity threshold.
One must bear in mind that the temperature sensitivity threshold is determined on the basis of continuous exposure to the heating medium, for one can tolerate much higher heat levels when one is only exposed momentarily or intermittently to high temperatures.
The temperature sensitivity threshold depends on the nature of the heating medium. Thus, as noted in the Lehmann text, when the medium is hot water which is at the same temperature and is applied to the patient in the same fashion as heated paraffin which has a low heat capacity, the paraffin can be tolerated by a patient but the hot water is intolerable for it has a high specific heat and a high order of thermal conductivity.
As a consequence, with conventional heating techniques, regardless of the medium used, when the patient is continuously exposed to a heating medium which is at a substantially constant temperature level, though this level is high enough to bring about adequate heat transfer to the problem region underlying the exposed skin, then the skin temperature is usually well above the tolerable level and this may result in extreme discomfort to the patient and even to the burning of tissue.
Because in all conventional heat applicators, the heat is applied continuously to the skin area overlying the problem region, this imposes strict limits on the acceptable temperature level. Thus if one seeks to have the heat penetrate more deeply into the body, the temperature at the surface area must be raised to promote more rapid heat transfer, for the higher the differential between the internal and external temperatures, the greater the rate of transfer. But a point is then quickly reached at which the patient is made uncomfortable for one can only tolerate continuously applied heat whose temperature level is not excessively above body temperature. The temperature sensitivity threshold for a given patient is that temperature level of the heating medium to which the patient is continuously exposed above which the patient experiences serious discomfort.
The prior Guibert U.S. Pat. No. 4,667,658 and our above-identified application disclose a technique for applying therapeutic heat to a skin surface area of a patient whose threshold of sensitivity is determined by that temperature level of the heating medium to which the patient is continuously exposed, above which the patient experiences discomfort or injury. In this technique, the skin surface is exposed to a heating medium whose temperature is at a base level that is well above ambient bug no higher than the temperature sensitivity threshold, the temperature of the medium being periodically raised above the base level to create high heat energy pulses whose peak temperatures are much higher than the threshold.
The duty cycle of these pulses is such as to allow for internal heat transfer to take place in the region below the exposed area of the patient in the intervals between pulses to an extent preventing an excessive rise in temperature at the skin surface whereby the patient gains the benefit of high heat energy treatment without discomfort or injury.
The topical application of a pharmaceutical cream, ointment or other agent to the surface of the skin overlying a problem region for the purpose of relieving pain or to alleviate an abnormal condition is commonplace. It is also known to adhere a patch to the skin, the patch being impregnated with a pharmaceutical agent that is absorbed and penetrates the tissue underlying the skin to interact therewith.
The present invention involves the application of heat energy to the same skin surface to which a pharmaceutical agent has been applied, the heat acting to render the tissue of the problem region more conducive to interaction with the agent. The present invention will be described in conjunction with a lipolysis cream that when applied to the skin in the area of the thighs, hips or buttocks, is absorbed and diffused throughout the tissues underlying the skin to bring about a reduction in cellulite fat deposits in these regions. It is to be understood, however, that this invention is by no means limited to a lipolysis cream and is unseable with any cream or ointment applied to the skin or to patch adhered to the skin in which the interaction of the pharmaceutical agent which is absorbed by the skin and penetrates the underlying tissue region is accelerated and promoted by the application of pulsed heat to the same surface.
U.S. Pat. No. 4,525,359 discloses a lipolysis cream which when applied to the skin in the hip, thigh or buttocks area, then penetrates the underlying tissue and interacts with fat deposits therein to bring about a reduction in these deposits, thereby reducing the weight of the individual body treated.
As pointed out in this patent, the in vivo neurological control of lipolysis in the fat cells is so organized that activity of the beta adrenergic receptor stimulates lipolysis, that is the hydrolysis of fat. An agent which activates the beta adrenergic receptor encourages lipolysis and results in the reduction in size of the fat cells. The beta adrenergic stimulator is selected from a group including theophylline, isoproternal, forskolin and eponephrine.